P4HA3 (Prolyl 4-Hydroxylase Subunit Alpha 3)

Inhibitors targeting P4HAs or P4HB have demonstrated promising anti-tumor effects, highlighting its potential as a therapeutic target. This review consolidates recent advancements in the comprehension of the roles and regulatory mechanisms of C-P4H in cancer progression and evaluates the development of C-P4H targeted therapies for prospective cancer treatment.

Frequently recovered proteins (e.g. P4HA3, SNX1, HIP1R, NOS2) are known to play key roles in lung cancer, highlighting the biological and clinical relevance of Protrec2. These findings establish Protrec2 as a robust, biologically grounded tool for missing protein recovery, with broad applicability in discovery proteomics and translational research.

ACLY-derived acetyl-CoA enhances H3K27 acetylation (H3K27ac) modification level in the promoter of SLC7A11 gene, ultimately enhancing SLC7A11 transcription and ferroptosis resistance. Collectively, our study provides a mechanistic understanding of the interplay between ferroptosis resistance and lymph node metastasis, providing a possibility to combat lymph node metastasis in cervical cancer.

Functional testing of domain 506-514 on breast cancer epithelial cells showed proliferation, chemotaxis and cell signaling response dependent on site localization of proline hydroxylation within domain 506-514 variants. These findings support site localized collagen HYP forms novel bioactive domains that are spatially distributed within the breast cancer microenvironment and may play a role in ancestral traits of breast cancer.

As collagen has a well-known association with tissue stiffness and aggressive forms of breast cancer, we believe that the two genes we identified provide an opportunity for a new therapeutic strategy in IntClust-2 breast cancers. Implications: Breast cancers with 11q13/14 chromosomal amplifications may be vulnerable to inhibitors of collagen synthesis.

Overall, given their essential roles in fundamental cellular processes and their involvement in disease mechanisms, PWWP2A and PWWP2B proteins could be ideal targets for therapeutic intervention. Thus, these proteins occupy a prominent position in the human proteome and epigenetic landscape.

Tubuloside A promotes the ubiquitin-proteasome degradation of P4HA3, exerting anti-CRC effects. In summary, our findings demonstrate that P4HA3 protects CRC cells from ferroptosis by regulating ACSL4 mRNA stability via AUF1, and Tubuloside A serves as a potential P4HA3 degrader, offering a promising therapeutic strategy for CRC treatment.

Moreover, P4HA3 deficiency inhibited the proliferation, migration and invasion abilities of tumor cells, and promoted anti-tumor immunotherapy of PD-1/PD-L1 inhibitor. This pan-cancer analysis of P4HA3 provides a comprehensive understanding of its oncogenic and prognosis role in different cancers, P4HA3 abnormal expression could be a useful biomarker for predicting the effectiveness of immunotherapy in cancer patients.

Furthermore, we confirmed that P4HA3 expression was strongly correlated with immune infiltrating cells, immune infiltration markers, the tumor mutational burden (TMB), microsatellite instability (MSI), the immune score, the stromal score, and immune checkpoints, thus highlighting P4HA3 as a crucial and dependable therapeutic target within the context of immune-based antitumor strategies. Our findings suggest that P4HA3 may function as an immune-related biomarker in the pathogenesis and treatment of GC, indicating that P4HA3 is a promising prognostic and therapeutic target for this malignancy.

In summary, we demonstrated that P4HA3 is a promising diagnostic and therapeutic biomarker for HNSCC. As an oncogene, P4HA3 increases HNSCC proliferation by inducing the EMT and activating the WNT/β-catenin signaling pathway.

Lastly, patients with CRC co-expressing P4HA3 and PD-1 had a significantly worse prognosis. High expression of P4HA3 is associated with adverse clinical features and immune cell infiltration in CRC, and has the potential to serve as a biomarker for predicting CRC prognosis.

Correlation experiments confirmed that P4HA1 may serve as a prognosis biomarker and plays a role in the progression of nasopharyngeal carcinoma. These findings suggest that P4HA1-3 may be a novel biomarker for the prognosis and treatment of HNSC, which is expected to support the development of new therapies for patients with head and neck tumors and improve patient outcomes.